New Insights into Vaginal Environment During Pregnancy

During pregnancy, the vaginal ecosystem undergoes marked changes, including a significant enrichment with Lactobacillus spp. and profound alterations in metabolic profiles. A deep comprehension of the vaginal environment may shed light on the physiology of pregnancy and may provide novel biomarkers...

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Main Authors: Antonella Marangoni, Luca Laghi, Sara Zagonari, Giulia Patuelli, Chenglin Zhu, Claudio Foschi, Sara Morselli, Maria Federica Pedna, Vittorio Sambri
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2021.656844/full
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author Antonella Marangoni
Luca Laghi
Sara Zagonari
Giulia Patuelli
Chenglin Zhu
Claudio Foschi
Sara Morselli
Maria Federica Pedna
Vittorio Sambri
Vittorio Sambri
author_facet Antonella Marangoni
Luca Laghi
Sara Zagonari
Giulia Patuelli
Chenglin Zhu
Claudio Foschi
Sara Morselli
Maria Federica Pedna
Vittorio Sambri
Vittorio Sambri
author_sort Antonella Marangoni
collection DOAJ
description During pregnancy, the vaginal ecosystem undergoes marked changes, including a significant enrichment with Lactobacillus spp. and profound alterations in metabolic profiles. A deep comprehension of the vaginal environment may shed light on the physiology of pregnancy and may provide novel biomarkers to identify subjects at risk of complications (e.g., miscarriage, preterm birth). In this study, we characterized the vaginal ecosystem in Caucasian women with a normal pregnancy (n = 64) at three different gestational ages (i.e., first, second and third trimester) and in subjects (n = 10) suffering a spontaneous first trimester miscarriage. We assessed the vaginal bacterial composition (Nugent score), the vaginal metabolic profiles (1H-NMR spectroscopy) and the vaginal levels of two cytokines (IL-6 and IL-8). Throughout pregnancy, the vaginal microbiota became less diverse, being mainly dominated by lactobacilli. This shift was clearly associated with marked changes in the vaginal metabolome: over the weeks, a progressive reduction in the levels of dysbiosis-associated metabolites (e.g., biogenic amines, alcohols, propionate, acetate) was observed. At the same time, several metabolites, typically found in healthy vaginal conditions, reached the highest concentrations at the end of pregnancy (e.g., lactate, glycine, phenylalanine, leucine, isoleucine). Lower levels of glucose were an additional fingerprint of a normal vaginal environment. The vaginal levels of IL-6 and IL-8 were significantly associated with the number of vaginal leukocytes, as well as with the presence of vaginal symptoms, but not with a condition of dysbiosis. Moreover, IL-8 concentration seemed to be a good predictor of the presence of vaginal Candida spp. Cytokine concentrations were negatively correlated to lactate, serine, and glycine concentrations, whereas the levels of 4-hydroxyphenyllactate, glucose, O-acetylcholine, and choline were positively correlated with Candida vaginal loads. Finally, we found that most cases of spontaneous abortion were associated with an abnormal vaginal microbiome, with higher levels of selected metabolites in the vaginal environment (e.g., inosine, fumarate, xanthine, benzoate, ascorbate). No association with higher pro-inflammatory cytokines was found. In conclusion, our analysis provides new insights into the pathophysiology of pregnancy and highlights potential biomarkers to enable the diagnosis of early pregnancy loss.
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spelling doaj.art-870eee173b1c48e8843df47640a743022022-12-21T21:29:48ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-05-01810.3389/fmolb.2021.656844656844New Insights into Vaginal Environment During PregnancyAntonella Marangoni0Luca Laghi1Sara Zagonari2Giulia Patuelli3Chenglin Zhu4Claudio Foschi5Sara Morselli6Maria Federica Pedna7Vittorio Sambri8Vittorio Sambri9Microbiology, DIMES, University of Bologna, Bologna, ItalyCentre of Foodomics, Department of Agro-Food Science and Technology, University of Bologna, Cesena, ItalyFamily Advisory Health Centres, Ravenna, ItalyFamily Advisory Health Centres, Ravenna, ItalyCentre of Foodomics, Department of Agro-Food Science and Technology, University of Bologna, Cesena, ItalyMicrobiology, DIMES, University of Bologna, Bologna, ItalyMicrobiology, DIMES, University of Bologna, Bologna, ItalyUnit of Microbiology, Greater Romagna Hub Laboratory, Pievesestina, ItalyMicrobiology, DIMES, University of Bologna, Bologna, ItalyUnit of Microbiology, Greater Romagna Hub Laboratory, Pievesestina, ItalyDuring pregnancy, the vaginal ecosystem undergoes marked changes, including a significant enrichment with Lactobacillus spp. and profound alterations in metabolic profiles. A deep comprehension of the vaginal environment may shed light on the physiology of pregnancy and may provide novel biomarkers to identify subjects at risk of complications (e.g., miscarriage, preterm birth). In this study, we characterized the vaginal ecosystem in Caucasian women with a normal pregnancy (n = 64) at three different gestational ages (i.e., first, second and third trimester) and in subjects (n = 10) suffering a spontaneous first trimester miscarriage. We assessed the vaginal bacterial composition (Nugent score), the vaginal metabolic profiles (1H-NMR spectroscopy) and the vaginal levels of two cytokines (IL-6 and IL-8). Throughout pregnancy, the vaginal microbiota became less diverse, being mainly dominated by lactobacilli. This shift was clearly associated with marked changes in the vaginal metabolome: over the weeks, a progressive reduction in the levels of dysbiosis-associated metabolites (e.g., biogenic amines, alcohols, propionate, acetate) was observed. At the same time, several metabolites, typically found in healthy vaginal conditions, reached the highest concentrations at the end of pregnancy (e.g., lactate, glycine, phenylalanine, leucine, isoleucine). Lower levels of glucose were an additional fingerprint of a normal vaginal environment. The vaginal levels of IL-6 and IL-8 were significantly associated with the number of vaginal leukocytes, as well as with the presence of vaginal symptoms, but not with a condition of dysbiosis. Moreover, IL-8 concentration seemed to be a good predictor of the presence of vaginal Candida spp. Cytokine concentrations were negatively correlated to lactate, serine, and glycine concentrations, whereas the levels of 4-hydroxyphenyllactate, glucose, O-acetylcholine, and choline were positively correlated with Candida vaginal loads. Finally, we found that most cases of spontaneous abortion were associated with an abnormal vaginal microbiome, with higher levels of selected metabolites in the vaginal environment (e.g., inosine, fumarate, xanthine, benzoate, ascorbate). No association with higher pro-inflammatory cytokines was found. In conclusion, our analysis provides new insights into the pathophysiology of pregnancy and highlights potential biomarkers to enable the diagnosis of early pregnancy loss.https://www.frontiersin.org/articles/10.3389/fmolb.2021.656844/fullvaginal microbiomevaginal metabolomepregnancymiscarriagewomen’s health
spellingShingle Antonella Marangoni
Luca Laghi
Sara Zagonari
Giulia Patuelli
Chenglin Zhu
Claudio Foschi
Sara Morselli
Maria Federica Pedna
Vittorio Sambri
Vittorio Sambri
New Insights into Vaginal Environment During Pregnancy
Frontiers in Molecular Biosciences
vaginal microbiome
vaginal metabolome
pregnancy
miscarriage
women’s health
title New Insights into Vaginal Environment During Pregnancy
title_full New Insights into Vaginal Environment During Pregnancy
title_fullStr New Insights into Vaginal Environment During Pregnancy
title_full_unstemmed New Insights into Vaginal Environment During Pregnancy
title_short New Insights into Vaginal Environment During Pregnancy
title_sort new insights into vaginal environment during pregnancy
topic vaginal microbiome
vaginal metabolome
pregnancy
miscarriage
women’s health
url https://www.frontiersin.org/articles/10.3389/fmolb.2021.656844/full
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